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Circ Res. 2011 Jan 21;108(2):210-8. doi: 10.1161/CIRCRESAHA.110.231258. Epub 2010 Dec 9.

Quarky calcium release in the heart.

Author information

1
Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, MD, USA. dbrochet@umaryland.edu

Abstract

RATIONALE:

In cardiac myocytes, "Ca(2+) sparks" represent the stereotyped elemental unit of Ca(2+) release arising from activation of large arrays of ryanodine receptors (RyRs), whereas "Ca(2+) blinks" represent the reciprocal Ca(2+) depletion signal produced in the terminal cisterns of the junctional sarcoplasmic reticulum. Emerging evidence, however, suggests possible substructures in local Ca(2+) release events.

OBJECTIVE:

With improved detection ability and sensitivity provided by simultaneous spark-blink pair measurements, we investigated possible release events that are smaller than sparks and their interplay with regular sparks.

METHODS AND RESULTS:

We directly visualized small solitary release events amid noise: spontaneous Ca(2+) quark-like or "quarky" Ca(2+) release (QCR) events in rabbit ventricular myocytes. Because the frequency of QCR events in paced myocytes is much higher than the frequency of Ca(2+) sparks, the total Ca(2+) leak attributable to the small QCR events is approximately equal to that of the spontaneous Ca(2+) sparks. Furthermore, the Ca(2+) release underlying a spark consists of an initial high-flux stereotypical release component and a low-flux highly variable QCR component. The QCR part of the spark, but not the initial release, is sensitive to cytosolic Ca(2+) buffering by EGTA, suggesting that the QCR component is attributable to a Ca(2+)-induced Ca(2+) release mechanism. Experimental evidence, together with modeling, suggests that QCR events may depend on the opening of rogue RyR2s (or small cluster of RyR2s).

CONCLUSIONS:

QCR events play an important role in shaping elemental Ca(2+) release characteristics and the nonspark QCR events contribute to "invisible" Ca(2+) leak in health and disease.

PMID:
21148431
PMCID:
PMC3036985
DOI:
10.1161/CIRCRESAHA.110.231258
[Indexed for MEDLINE]
Free PMC Article
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